1. Field of the Invention
The present invention relates to a method for measuring respiratory drive from breath waveforms using peak inspiratory flow and acceleration. The present invention also relates to an inductive plethysmographic system with a rapid sampling rate and a reduced signal to noise ratio that diminishes variability in the new measures of respiratory drive among other applications. The present invention further relates to the use of an inductive plethysmographic system as a trigger for initiating mechanical ventilator inflation and the use of the two measures of respiratory drive along with breath waveform shape to control the level of continuous positive airway pressure (CPAP) to eliminate obstructive sleep apneas and increased upper airway resistance during sleep.
2. Description of the Related Art
Breath waveforms and patterns of breathing are shaped and modulated, respectively, by neural discharges to the respiratory muscles from the respiratory center in the brain and the response to those impulses by respiratory muscles acting upon mechanical components of the respiratory system. Devices that provide analog waveforms of breathing, such as spirometers or pneumotachographs, have been utilized to provide information on respiratory drive that originates from the brain and the mechanical factors affecting configuration of the breath waveforms.
The most direct representation of respiratory center activity or "drive" to the respiratory muscles is the diaphragmatic electromyogram (Edi). The rate of rise (mean slope) of the moving time averaged Edi (mtaEdi) gives the most consistent results as a measure of drive, as is reflected by the highest correlation coefficients from plots against ventilation during CO.sub.2 rebreathing which is a procedure that stimulates the respiratory center. However, measuring of the Edi involves the technically difficult and uncomfortable placement of an electrode catheter within the esophagus of a patient followed by blind trial and error movements of the catheter upward and downward until a point is reached at which maximum electromyogram activity synchronous with inspiration is identified. This measure has a high failure rate due to inability to locate a site with acceptable diaphragmatic electromyogram activity.
Because of technical and invasive shortcomings of the above-described esophageal electrode procedure for collecting moving time average Edi (mtaEdi), less invasive, indirect methods for estimation of respiratory drive have been tested. These alternate methods include determination of the mechanical analog of mtaEdi from the breath waveform using mean inspiratory flow (VtTi) and the mouth occlusion pressure (P0.1).
In normal circumstances, increased respiratory drive causes an increase in ventilation manifested by increased respiratory rate and tidal volume. However, increased respiratory drive may fail to increase ventilation when the mechanical properties of the respiratory system are impaired, such as when there is a high-grade respiratory obstruction. In extreme cases, as typified by obstructive apnea in which the respiratory system is fully blocked, respiratory efforts manifested by paradoxical movements of the rib cage and abdomen indicate that neural discharges from the respiratory center to the respiratory muscles take place. Because of obstructions, however, no air flows in the respiratory system. In this case, the analog breath waveforms from devices that measure breathing patterns at the airway by displacement of volume or flow, such as spirometers or pneumotachographs, respectively, do not detect the presence of respiration or drive. The waveforms from these devices are flat lines. Thus, the use of measurement of Vt/Ti as a measure of drive has limited applications in clinical practice.
Mouth occlusion pressure (i.e. the pressure developed 100 ms after an unanticipated inspiratory occlusion of the airway) has also been advocated as a robust test of respiratory drive. This process detects drive during complete airway obstruction but has a number of shortcomings. It is affected by the lung volume in which occlusion is carried out so that comparisons in a given trial can only be made if lung volume is held constant. In addition, P0.1 underestimates pressure in a nonlinear way because there are pressure losses due to the is parallel compliance of the neck and oropharynx in the respiratory system; this problem can be minimized by using esophageal rather than mouth pressure but this then makes the test invasive and less clinically acceptable. Moreover, pressure measurements from both these sites have inherent inaccuracies due to difficulties in discerning the start of inspiration from the pressure waveforms.
Studies that have measured P0.1 simultaneously in the mouth and esophagus in Chronic Obstructive Pulmonary Disease (COPD) patients during CO.sub.2 rebreathing to ascertain whether either of these measurements reflects central respiratory drive found considerable variability between the pressure measured at the mouth (Pm) and the pressure measured at the esophagus (Pes) in CO.sub.2 rebreathing as well as in the time difference between the two. There is significant difficulty in defining the onset of inspiration from Pes and Pm because often they lack a distinct onset of inspiration. Also, in the presence of intrinsic Positive End Expiratory Pressure (PEEP), as may occur in COPD patients, the neural onset of inspiration may differ from the mechanical onset. Recording of the external electromyogram signal may help to clarify the neural onset of inspiration, but electromyogram electrodes only record from the underlying muscle groups, and different muscle groups may be activated at different times again obscuring the time of inspiratory onset. The problem of determining the true onset of inspiratory muscle activity. from pressure data, and the likelihood that breaths are taken from different lung volumes, make it unlikely that either Pes0.1 or Pm0.1 actually represents drive in COPD.
Despite its limitations, P0.1 as a measure of drive has provided insight into the mechanism of the sensation of uncomfortable breathlessness for a given exercise activity, also known as dyspnea, which is a prominent symptom of cardiopulmonary disorders. It has been postulated that "length-tension inappropriateness" might be the cause of such breathlessness. If the length attained in the respiratory muscles were inappropriate for the tension produced relative to the patient's previous experience, the sensation of breathlessness ensues. In other words, for the amount of tension developed in the inspiratory muscles the expansion of the chest is less than expected; this statement was later modified to include "mechanical inappropriateness" such as phasic distortions of the respiratory system as other factors that might contribute to dyspnea. In clinically testing this assertion, an analogy was drawn between ". . . the amount of tension developed in the respiratory muscles" to P0.1 and between ". . . expansion of the chest" to ventilation. It was found that the ratio of ventilation to P0.1 at rest was significantly less in breathless as compared to non-breathless resting COPD patients: 3.7 vs 6.3 (p&lt;0.01). Breathlessness was not related to the level of arterial blood gases to oxygen consumption, nor minute ventilation and respiratory rate.
In a follow-up study, the relation of respiratory drive as measured by the ratio of P0.1/Ventilation in 84 seated, resting, healthy subjects and 79 patients with either COPD (n=63) or restrictive lung disease (n=16) was analyzed. It was confirmed that resting drive as measured by P0.1 was greater in patients with lung disease than normal subjects. However, because of large intra- and interindividual variability of P0.1, there was wide overlap between the values for normal subjects and patients. Since minute ventilation is a direct consequence of respiratory drive, in each individual there was a linear relation between ventilation and P0.1. Therefore, P0.1 may be considered the input and ventilation the output of the respiratory pump. Any perturbation in mechanics of the respiratory pump, i.e. lungs and/or chest bellows, alters this relationship. The ratio of ventilation/P0.1 can be expected to provide information not only on the level of resting drive but on the state of respiratory mechanics and appropriateness or inappropriateness of drive. The study found that the ratio was unaltered by age or sex in normal subjects and sharply demarcated those with normal pulmonary function from patients with lung disease. In 99% of normal subjects, Ventilation/P0.1 was &lt; 8 whereas in only one of 79 lung. disease patients was the value &lt; 7.9. The authors of the study cautioned that measurement of P0.1 and ventilation be made at the same recording session because errors could arise if the measurements were separated temporarily owing to moment to moment variations in these parameters.
The increased respiratory drive and reduced efficiency of ventilation appear to be related to the flattened diaphragmatic muscle that becomes an ineffective force generator in COPD patients, a hallmark of the disease. It is known that patients with severe COPD have an increased neural drive to the intercostal and accessory muscles of respiration and greater inspiratory expansion of the rib cage than do healthy subjects. They also have reduced outward expansion or paradoxical inward displacement of the ventral abdontinal wall during inspiration, meaning that diaphragmatic excursions are reduced. Discharge diaphragmatic electromyographic frequencies from diaphragmatic motor units revealed that these patients also had increased neural is drive to the diaphragm. Consequently, the reduced inspiratory expansion of the abdomen in severe COPD results from mechanical limitation of diaphragmatic contractions alone. The phenomenon in COPD patients can be simulated in normal subjects by allowing them to breathe against a pressure load, i.e. PEEP (Positive End Expiratory Pressure) of 5 to 10 cm H.sub.2 O during expiration. This causes the diaphragm to descend from its normal position at end-expiratory level (EELV) and to have a flattened shape as in patients with COPD as detected by an elevated EELV.
The sensory experience of breathlessness during exercise between normal subjects and COPD patients was compared. Breathlessness was qualitatively different between exercising normal subjects and COPD patients. Regression analysis revealed that the ratio of esophageal (pleural) pressure/maximum voluntary pressure (drive measure) to tidal volume/predicted vital capacity (ventilation measure) was the strongest correlate of a standardized Borg scale of subjective breathlessness. The latter also strongly correlated with the ratio of dynamic end expiratory lung volume level to total lung capacity. The authors of this study concluded that the qualitatively discrete respiratory sensations of exertion inspiratory difficulty peculiar to COPD patients may have their origins in dynamic pulmonary hyperinflation and the resultant disparity between respiratory effort and ventilatory output.
It has also been found that respiratory symptoms and degree of airway obstruction measured with spirometry correlated poorly in adult asthmatics with moderate to severe asthma. The authors stated that the results support the recommendation that airway obstruction should be measured objectively when assessing adult patients with bronchial asthma. However, an opposite conclusion can be drawn from the study. At both rest and exercise, there is evidence that a dynamic hyperinflation of the lung correlates well with symptoms. This causes elevation of the respiratory drive to ventilation ratio (or decrease in the ventilation to respiratory drive ratio), which is compatible with the above mentioned length-tension inappropriateness theory of breathlessness.
As indicated in the preceding discussion, there are major problems with current techniques for measuring respiratory drive and ventilation. For clinical relevance, the method should ideally utilize non-invasive technology, have the capability for discrete or continuous monitoring, and analyze breath waveforms with a simple algorithm to obtain drive and ventilation simultaneously on a breath by breath or one minute average. Moving time average diaphragmatic electromyogram (mtaEdi), the "gold standard" for respiratory drive, requires insertion of an esophageal catheter, an invasive procedure reserved for research applications that cannot have widespread clinical use. Moreover, another device is needed to collect ventilation. P0.1 estimations cannot be used for continuous measurements and are problematic in terms of accuracy because of the difficulty in choosing the exact onset of inspiration from the pressure waveform, particularly in COPD patients; furthermore, a separate technology is still required for measurement of ventilation. Mean inspiratory flow (Vt/Ti) fails to track respiratory drive when the respiratory system is subjected to high resistive loading.
The standard measure of breathing pattern that measures respiratory drive, mean inspiratory flow (Vt/Ti), does not reflect drive in the presence of high grade resistive loading or during complete obstruction of the airway as in obstructive sleep apneas. Occlusion pressure, i.e. P0.1, measures drive during obstructed breathing but requires a pressure sensor at the airway proximal to the site of obstruction. This system can be used in the laboratory for discrete measurements but cannot be utilized well in sleeping or critically ill patients where continuous data is preferred. The technology has questionable accuracy in patients with COPD. Diaphragmatic electromyographic measurements of drive require insertion of an esophageal catheter and noise-free data are technically difficult to obtain. The measure is impractical for long term monitoring. Therefore, it would be desirable to have a parameter of respiratory drive that can provide noninvasive, continuous measurements during high-grade resistive and elastic loading of the respiratory system.
A non-invasive technology that can measure drive and ventilation by current methods from breath waveforms is the respiratory inductive plethysmograph. It measures breath by breath ventilation from the results of multiplication of the tidal volume by rate and it computes respiratory drive by dividing tidal volume by inspiratory time to provide the mean inspiratory flow parameter (Vt/Ti). Unfortunately, as mentioned above, Vt/Ti is a not a good indicator of drive in high grade respiratory loading situations, as may for example occur with severe bronchospasm or obstructive hypopneas, and fails to track drive at all in obstructive apneas since Vt has a value of zero during mechanical respiratory efforts.
In recent years, attention has been directed toward methods for triggering initiation of inspiratory inflations by mechanical ventilators. For babies, the concern has related to the delay and desynchronization owing to the rapid breathing rates, intrinsic airway resistance, and transmission of the pressure trigger (PT) or flow trigger (FT) pulse from the measurement site of the trigger to the respirator. This delay that leads to asynchrony between spontaneously breathing mechanically ventilated infants and the ventilator has been associated with pneumothorax, intracranial hemorrhage, and hemodynamic instability. To minimize trigger delay in babies, trigger pulses obtained from sensors placed on the body surface, such as the Grasby capsule, (an applanation device on the abdominal wall), and the impedance pneumograph, have been utilized as alternatives to devices on the airways. In adults, the major concern dealing with triggering the effects of intrinsic PEEP and delay in initiation of the ventilator breath involves overcoming PEEP with the consequence of an increase in the work of breathing. Measurements of trigger effectiveness in terms of delay, failure to trigger, and work of breathing have been made in models and patients.
FIG. 15 illustrates the considerations in computing the delay in the presence of intrinsic PEEP; FIG. 15 is reproduced from FIG. 1 in the paper by S. Nava, N. Ambrosino, C. Bruschi, M. Confalonieri, and C. Rampulla. Physiological Effects of Flow and Pressure Triggering During Non-Invasive Mechanical Ventilation In Patients With Chronic Obstructive Pulmonary Disease, 52 Thorax 249-254 (1997). From top to bottom, FIG. 15 depicts flow, esophageal pressure, and airway pressure. The two solid lines identify, on the esophageal pressure trace, the inspiratory effort during pre-triggering. The initial portion of esophageal pressure, between the onset of the negative deflection and the point corresponding to the crossing of zero flow (dashed line), represents the effort to overcome intrinsic PEEP. The second portion of the esophageal pressure trace, between zero flow crossing and the point of its abrupt rise (and maximum negative airway pressure), represents the effort to open the inspiratory valve of the mechanical ventilator.
In ventilated neonates, asynchrony between mechanical and spontaneous breaths may lead to impaired ventilation and gas exchange or to barotrauma. Synchronization of spontaneous and mechanical breaths increases tidal volume of mechanical breaths, reduces blood pressure fluctuations, and improves gas exchange. To synchronize ventilator-generated breaths with an infant's spontaneous breathing pattern, beginning inspiration must be acutely detected. If the response time is too long, mechanical inspiration might last into the spontaneous expiratory phase, or may even begin during expiration, which can potentially impair ventilation and gas exchange. Flow-triggered (FT) ventilators are one means to initiate inspiratory inflation of the lungs. In a study to compare the performance of an impedance trigger (IT) system with electrodes on the chest connected to the FT system, the median response time for the FT system was 115 (79-184) msec. whereas the median response time for the IT system was 169 (98-305) msec. The longer and more variable response of the impedance system was secondary to phase lag of the impedance signal caused by "chest wall distortion." Although 13% of mechanical breaths were autotriggered with the impedance system, there were no autotriggered breaths with FT.
The response time of three neonatal commercial respirators was also measured. The Draeger Babylog 8000 used flow triggering (FT) with hot wire anaemometer and a threshold of 5 ml/s. At the maximum sensitivity setting, the ventilator triggered on a spontaneous inspiratory volume 0.3 ml above the 5 ml/s flow. The Bear Cub Enhancement module has a hot wire anaemometer that serves as a flow trigger; at its maximum sensitivity, the flow rate is 1 ml/s. The Star Synch module of the InfantStar ventilator uses a Graseby pressure capsule on the abdomen as a trigger and does not have a threshold level. Recordings for response time were digitally sampled at 1000 points/s and for reliability at 200 points/s. The response time of the Star Sych was 53 (13), of the Bear Cub 65 (15) and of the Babylog 95 (24) msec.
Patient triggered ventilation (PTV) has been questioned for infants because of large trigger pressures and long delay times. Recently, four infant ventilators with flow triggering have become available; they were tested using an infant model lung simulator. The tests indicated that PTV may not be appropriate under conditions of increased ventilatory drive and small endotracheal tube in infants; e.g., the delay time was 138 msec. using a 3 mm endotracheal tube during high ventilatory drive. Delay times for any respirator, site (airway, trachea, alveolus) and diameter endotracheal tube (3 mm, 4 mm, 5 mm) were a minimum of 60 msec. The investigators concluded that PTV may not be appropriate under conditions of increased ventilatory drive and small endotracheal tube size in infants because of unacceptable delays in triggering the mechanical ventilator.
FIG. 16 illustrates how an increased resistance to flow, as might occur in patients with resistive airways disease or narrow endotracheal tubes, produces unacceptable delays in triggering mechanical ventilators from sensors placed at the airways. The recordings shown in FIG. 16 are of anesthetized monkey breathing through high resistors. MVt (tidal volume), mRC (rib cage), and mAB (abdomen) indicate Respitrace waveforms adjusted for filter delays so that timing is amatched for all traces. The true onset of inspiration is depicted from negative deflection of esophogeal (transpulmonary pressure-Ptp) and delayed onset of inspiration from the integrated pneumotachographic waveform (IPNT) in the presence of resistive loading. In this example, the delay in the onset of inspiration from the airway sensor would have been unacceptable as a trigger of an inspiratory breath from a mechanical ventilator. However, the signal from t he abdominal compartment (AB) respiratory inductive plethysmograph (Respitrace.TM.), since it was in phase with Ptp, would have been. Other traces in this recording are indices of thoracoabdominal coordination along with their numerical values.
For adults, data on flow triggering (FT) at 1 and 5 L/m and pressure triggering (PT) at 1 cm. H.sub.2 O during pressure support ventilation (PSV) and assist/control ventilation (A/C) delivered non-invasively through a full facemask to patients with COPD recovering from an acute exacerbation has also been reported. Minute ventilation, breathing pattern, dynamic lung compliance and resistance, and changes of end expiratory lung volume were the same with the two triggering systems. Measurements dealing with the work of breathing were lower with FT than PT in both PSV and A/C modes; this was because intrinsic PEEP was reduced and the time of valve opening was sooner with FT. Flow triggering (FT) more consistently reduced breathing effort than pressure triggering (PT) when used in conjunction with PSV than with constant flow assist/control ventilation. It has been reported that significant advances in this area may have to await the development of technology that enables ventilator triggering from signals closer to the patient, such as esophageal pressure. In this regard, FIG. 16 indicates that the inspiratory onset of the abdominal compartment expansion using a Respitrace.TM., or any other type of device that measures cross-section area or circumference, may fulfill that need. In certain situations, the inspiratory onset of RC expansion may also serve as a suitable trigger.
Continuous positive airway pressure (CPAP), usually delivered via a nasal mask from an air source with capability for adjustment of the pressure, is utilized in the treatment of obstructive sleep apnea syndrome and the "upper airway resistance syndrome." This treatment splints the upper airway and eliminates or minimizes obstructive apneas and hypopneas, and diminishes partial upper airways obstructions (upper airway resistance syndrome). The first commercially available CPAP devices had pressure controls that could be set to a fixed value. Usually, patients with obstructive sleep apnea syndrome were studied in a sleep laboratory and pressures were adjusted by personnel to a level where apneas were eliminated or greatly reduced in frequency. The patient then utilized this set pressure in a CPAP device at his/her home setting. With recognition that a spectrum of airway obstructions exists in obstructive sleep apnea syndromes which vary throughout the night--ranging from complete obstruction, apnea, to partial obstruction as exemplified by hypopneas and the "upper airway resistance syndrome"--this treatment has been reevaluated. Even partial obstructions can cause arousals and sleep deprivation leading to daytime hypersomnolence, a hallmark of respiratory related sleep disturbances.
CPAP devices have been devised to automatically modify the level of pressure applied through analysis of the shape of the inspiratory flow waveform and detection of apneas through flow measuring devices on the inspiratory and expiratory ports of these devices. It has been known for many years that an inspiratory flow waveform has a sinusoidal shape in unobstructed breathing and is flattened or rectangularly shaped in the presence of inspiratory upper airways obstruction. The shape of the inspiratory flow pattern can be expressed as a numerical index by dividing peak inspiratory flow by mean inspiratory flow (PIF/MF). A sinusoidal shaped inspiratory flow waveform that is indicative of unobstructed breathing has a PIF/MF value of pie/2=3.14/2=1.57. A perfect rectangularly shaped, inspiratory flow waveform has a PIF/MF value of 1.0. Significant flattening from a sinusoidal shape occurs at a PIF/MF value of about 1.3 and below.
Variants of this index have been used to continuously compute the index and adjust CPAP pressures as a damped closed loop response. These devices may also incorporate a microphone as a snoring indicator and adjust the level of CPAP in response to snoring sounds. Apneas are also detected and the level of CPAP can be adjusted accordingly. Air leaks in the system or mask-face or nasal prongs-nasal interfaces are detected as a discrepancy between the inspiratory volume delivered by the CPAP device versus the value recorded at the expiratory part as a measure of quality control.
A new self-titrating CPAP device recently introduced into commerce monitors the device rather than the patient. High pressures within the tubing leading to the mask can lead to loss of volume delivered to the patient as a function of the compliance of the tubing and such volumes are not accounted for. Leaks at the mask-face interface cannot be accurately measured. If the CPAP mask or CPAP nasal prongs (used as a means to deliver CPAP to infants) slips off the face, all data from breathing are thereafter lost to monitoring and analysis. Pneumotachographs, i.e. flow measuring devices placed within the inspiratory and expiratory ports of these devices, may be inaccurate because accuracy suffers when they are put in line with high system pressures. Furthermore, such devices cannot accurately distinguish central from obstructive apneas.